Patterns of quantitative sensation testing of hypoesthesia and hyperalgesia are predictive of diabetic polyneuropathy - A study of three cohorts

OBJECTIVE - To test quantitative sensation testing (QST) patterns of hypoesthesia and hyperalgesia as indicators of diabetic polyneuropathy (DPN) and its severity. RESEARCH DESIGN AND METHODS - We used Computer-Assisted Sensory Examination IV; characterized the QST results of the foot of each patient in three diabetic cohorts (similar to 1,500 patients) as hyperesthetic (less than or equal to 2.5th percentile), low-normal (2.5th-50th percentiles), high-normal (50th-97.5th percentiles),or hypoesthetic (greater than or equal to 97.5th percentile); and tested associations with symptoms, impairments, and test abnormalities. RESULTS - Overall neuropathic impairment was most severe in the pancreas-renal transplant and nerve growth factor cohorts, but it was much less severe in the population-based Rochester Diabetic Neuropathy Study (RDNS) cohort. The frequency distribution of sensory abnormalities mirrored this difference. When the QST spectra of diabetic cohorts were compared with those of the control subject cohort for vibration and cooling sensations, the only abnormality observed was hypoesthesia, which was expressed as an increased number of subjects with values at or above the 97.5th percentile or by an increased percentage of cases with high-normal values. Symptoms and impairments of DPN were significantly more frequent in the subjects with Values at or above the 97.5th percentile than in the subjects whose values were between the 50th and 97.5th percentiles. For heat pain (HP) sensation thresholds (intermediate pain severity [HP:5], pain threshold [HP:0.5]. and pain-stimulus response slope [HP:5-0.5]), an increased frequency of both hypoalgesia and hyperalgesia was observed (especially in the RDNS cohort). Steeper pain-stimulus response slopes were significantly associated with sensory symptoms, including severity of pain. CONCLUSIONS - 1) Decreased vibratory sensation (hypoesthesia) appears to be characteristic of mild DPN, whereas pan-modality hypoesthesia is characteristic of severe DPN 2) A shift of vibratory and cold detection thresholds land also of attributes of nerve conduction and a measure of autonomic dysfunction) from low-normal (2.5th-50th percentiles) to high-normal (50th-37.5th percentiles) appears to precede overt expression of DPN and to thereby provide evidence of subclinical abnormality. 3) Heat stimulus-induced hyperesthesia (low thresholds) occurs especially in mild DPN, and, because it correlates with DPN symptoms and impairments, it must be attributed to hyperalgesia rather than to supersensitivity. Therefore, hypoalgesia or hyperalgesia may be an indicator of early DPN.